The present invention relates to stabilized preparations of active forms of vitamin D.sub.3.
Active derivatives of vitamin D.sub.3 represented by 1.alpha.,25-dihydroxyvitamin D.sub.3 and 1.alpha.-hydroxyvitamin D.sub.3 have the ability to improve calcium metabolism, especially bone metabolism, and find extensive clinical use not only in patients under blood dialysis therapy who suffer from bone diseases resulting from impaired vitamin D activity in kidneys but also in the treatment of diseases that are difficult to cure by conventional vitamin D.sub.3 drugs, such as chronic renal insufficiency, hypoparathyroidism, vitamin D-resistant rickets and osteomalacia. These active forms of vitamin D.sub.3 are also administered to premature babies to sustain their growth.
The active forms of vitamin D.sub.3 have such strong physiological activities that their single doses are limited to very small amounts. In order to ensure uniformity in their levels in preparations and their stability as well, the active forms of vitamin D.sub.3 are most often administered in the form of soft capsules filled with oily solutions such as middle-chain aliphatic acid triglycerides, or in the form of oily liquids.
Practicing doctors who are attending patients with chronic renal insufficiency see the strong need to develop injections of active forms of vitamin D.sub.3 that can be directly administered into the patient's blood during blood dialysis. Active forms of vitamin D.sub.3 administered in the form of oily liquids to premature babies and infants have the unpleasant taste of oils and cases have been reported that infants to whom the oily liquids had been repeatedly administered eventually refused to take further doses of the liquids. Oily liquids of active forms of vitamin D.sub.3 may be administered to infants in the form of mixtures with milk or fruit juice, but the oily liquids will not mix uniformly with milk or fruit juice and present considerable difficulty in maintaining the exact amount of dose since the formulation will partly stick to the inner surface of nursing bottles or cups. Stability test with active forms of vitamin D.sub.3, which are fat-soluble vitamins, after they were solubilized with a variety of solubilizers to form liquid preparations or made into tablets or fine particles with the aid of various excipients showed that these preparations were unable to remain stable and degraded quickly at room temperature.